Home

Patient FAQs on uveal melanoma treatment

Why are uveal melanomas treated?

Ocular treatment is aimed primarily at prolonging life by preventing metastatic spread of the tumour from the eye. Another objective is to to prevent the eye from becoming inflamed, red and painful. If possible, the eye is conserved with useful vision.

 

How are uveal melanomas treated?

The various forms of therapy are radiotherapy, surgical excision and phototherapy (i.e., light therapy).

 

How does radiotherapy work?

Radiotherapy damages the DNA of the tumour cells so that these can no longer multiply. If tumour cells cannot divide and rejuvinate they die of senescence (i.e., 'old age'). It takes time for tumour cells to become old and die, which is why melanomas shrink slowly after radiotherapy. The more slowly the tumour regresses, the slower the cellular turnover and the better the prognosis for survival, as several studies have shown.

 

How is radiotherapy delivered?

The main forms of radiotherapy for uveal melanoma are plaque radiotherapy, proton beam radiotherapy and stereotactic radiotherapy.

 

Plaque radiotherapy is delivered by means of a metal applicator, containing a radioactive source on its inner surface. This 'plaque' is sutured to the wall of the eye, directly adjacent to the tumour, and removed a few days later once the required dose of radiation has been delivered to the entire melanoma. Plaques containing radioactive ruthenium-106 can treat tumours up to 5 mm or 6 mm thick. Iodine-125 plaques can treat thicker tumours but at a cost of delivering toxic doses of radiation to healthy parts of the eye.

 

Proton beam radiotherapy is delivered with a cyclotron unit, which is an enormous 'gun' that bombards the tumour with protons. At present, there is only one cyclotron unit in Britain and this is located at Clatterbridge Centre for Oncology, near Liverpool. It receives patients from all over the UK and from overseas for treatment. The treatment is delivered in four sessions over four successive days. A dress-rehearsal is undertaken one day before the start of the treatment. To ensure that the beam is aimed accurately at tumours located at the back of the eye, four tiny buttons are sutured to the wall of the eye at known distances from the tumour. They are visible on x-ray examination so that they indicate the precise location of the tumour. These are implanted more than a week before the start of the radiotherapy and are usually left in place permanently.

 

With stereotactic radiotherapy, fine beams of radiation are aimed at the tumour from many different directions, either simultaneously or consecutively. This makes it possible to focus high doses of radiation at the tumour while minimising damage to surrounding healthy tissues.

 

How are uveal melanomas removed surgically?

The simplest and quickest way to excise a uveal melanoma is to to remove the eye (i.e., 'enucleation').

In some patients, the eye can be saved by removing the tumour in one piece through an opening in the wall of the eye. Iris tumours are removed by iridectomy, through a slit at the edge of the cornea. Choroidal tumours are removed by 'choroidectomy', through a large trapdoor in the wall of the eye. Ciliary body tumours are removed by 'cyclectomy', usually in combination with excision of part of the iris or choroid (i.e., 'iridocyclectomy' and 'choroidectomy' respectively). Choroidectomy is a very difficult procedure and requires profound hypotensive anaesthesia lowering the blood pressure to a third of normal levels.

 

With endoresection, the tumour is chopped up into many tiny fragments which are 'hoovered' away and this is done with a vitreous cutter, which is like a vacuum cleaner passed through a hole in the retina. This is a controversial operation because of fears that if any tumour fragments are left behind they will spread around the eye and to the rest of the body. These concerns are not borne out by quality-control studies.

 

How can light be used to treat uveal melanomas?

With trans-pupillary thermotherapy (TTT), an infra-red beam of light beam is directed at the tumour through the pupil to heat the target tissues by a few degrees for about one minute, so that the metabolic processes are disrupted. This is done using a contact lens and with the patient seated at a slit-lamp.

 

With photodynamic therapy (PDT), a weak beam of infra-red light is directed at the tumour through the pupil for about a minute and a half so as to activate a drug (i.e., 'photosensitizer'), which has been injected into a vein in the arm.

 

Photocoagulation is no longer used for uveal melanomas, because of complications. This involves directing a strong beam of light energy at the tumour so that the target tissues reach very high temperatures.

 

How effective is ocular treatment at preventing metastasis?

There are no hard data to prove that ocular treatment prevents metastatic spread. This would require comparisons between treated and untreated patients and it has not yet been possible to conduct such an experiment because of the very large numbers of patients that need to be enrolled and also because of ethical concerns.

 

Uveal melanomas showing monosomy 3 have a high mortality, with survival being particularly poor if the tumour is large. This suggests that metastatic spread commences very soon after monosomy 3 develops. It is not yet known whether ocular treatment ever prevents initial spread of tumour once monosomy 3 has occurred. More evidence is needed but hard to come by.

 

Very few if any uveal melanomas are fatal if they do not show monosomy 3. How many such tumours develop monosomy 3 if left untreated is not known. Some believe that monosomy 3 develops very early or not at all; however, there is circumstantial evidence that late transformation from disomy 3 to monosomy 3 can indeed occur, at least in some patients.

 

If the uveal melanoma is not causing any symptoms, should it be left untreated?

This is a very difficult decision and is to some extent a gamble (i.e., deciding without adequate evidence).

If the tumour has already metastasized, then metastatic disease is almost inevitable. Such disease may wrongly be attributed to non-treatment, causing regret. A tumour that has metastasized is likely to grow quickly and will probably need ocular treatment sooner or later to prevent the eye becoming blind and painful.

If the tumour has not metastasized and if it is of the disomy 3 type it may behave in a very indolent manner, growing slowly or not at all. If treatment is delayed then any side-effects from that treatment will also be delayed. The risk is that after months or years of indolent growth the tumour will suddenly grow quickly so that opportunities for conserving vision and preventing metastatic spread my be lost.

The decision as to whether or not to treat a melanoma is also influenced by the likelihood of treatmend causing loss of vision and other side-effects.

 

What are the advantages and disadvantages of the various forms of ocular treatment?

Plaque radiotherapy is

  • completed in a few days
  • does not damage the eyelids and outer surface of the eye

...but

  • can be difficult and unreliable with tumours located far back in the eye near the optic nerve
  • is not suitable for tumours exceeding a certain thickness
  • requires two operations, to insert and remove the applicator.

 

Proton beam radiotherapy is

  • easier to administer reliably with small tumours far back in the eye
  • more gentle to the surface of the eye than plaque radiotherapy when treating iris melanomas
  • possible with large tumours

...but

  • requires two trips to Clatterbridge Centre for Oncology, on the Wirral Peninsula
  • can cause damage to eyelids and the surface of the eye, with loss of lashes, irritation and redness.

 

Phototherapy

  • is quick and simple, completed in half an hour under local anaesthesia
  • does not damage the optic nerve
  • does not aggravate diabetic retinopathy, unlike radiotherapy

...but

  • is not as reliable as radiotherapy
  • is suitable only for very small tumours.

 

Trans-scleral choroidectomy

  • is possible with large tumours and, unlike radiotherapy, gets rid of the dead tumour so that it does not poison the eye
  • provides tissue for diagnosis and prognostication

...but

  • is difficult and associated with a significant risk of ocular complications, although these are usually treatable
  • requires profound hypotensive anaesthesia
  • is performed by only a few surgeons.

 

Endoresection

  • removes the tumour without damaging the optic nerve if this is nearby
  • provides tissue for diagnosis and prognostication

...but

  • is controversial because of concerns about disseminating tumour, although these seem exaggerated
  • requires a second operation to remove silicone oil and cataract, twelve weeks later
  • may require another two operations if microscopic examination indicates that plaque radiotherapy is also necessary

 

Iridectomy

  • is straightforward
  • provides tissue for diagnosis and prognostication

...but

  • causes a large iris defect with cosmetic deformity and intolerance to bright light

 

Iridocyclectomy

  • is not too difficult
  • provides tissue for diagnosis and prognostication
  • does not cause excessive pupil deformity if not much of the iris is involved

...but

  • requires an experienced surgeon

 

Enucleation

  • is quick and straightforward
  • provides tissue for diagnosis and prognostication
  • is unlikely to be followed by complications such as local tumour recurrence

...but

  • does not improve the chances of survival as compared to eye-conserving methods
  • results in loss of vision, inevitably
  • is undesirable to most patients.